The aim of the present study was to analyse, in segments of human placental veins, the effect of the Ca2+ channel agonist Bay K 8644 (0.1 microM) and Ca2+ channel antagonists nifedipine (0.1 microM) and diltiazem (1 microM) on vascular contractility and 45Ca2+ uptake. 2. The Ca2+ channel agonist Bay K 8644 (0.1 microM) caused small concentration dependent contractions that were increased by a moderate membrane depolarization with 7.5 mM K+. This increase was reversed by nifedipine and diltiazem. Ca2+ addition to segments previously depolarized with 75 mM K+ and exposed to a Ca(2+)-free medium caused contractile responses that were increased by 0.1 microM Bay K 8644; such an increase was blocked by 0.1 microM nifedipine and 1 microM diltiazem. 3. K+ and 5-HT induced concentration dependent contractile responses which were increased by Bay K 8644 (0.1 microM). Both 0.1 microM nifedipine and 1 microM diltiazem inhibited the increasing effect of Bay K 8644. Bay K 8644 (30 nM and 0.1 microM) caused an enhancement in 45Ca2+ accumulation over the basal value, that was increased by membrane depolarization with K+ (7.5, 15 and 30 nM) and inhibited by nifedipine (0.1 microM). K+ (15 and 30, but not 7.5 mM) and 5-HT (1 microM) induced 45Ca2+ uptake over the basal level that was increased by Bay K 8644 (0.1 microM). Such an increase was antagonized by nifedipine (0.1 microM). 4. These data indicate that: (1) a small depolarization with K+ is needed for Bay K 8644 to be able to produce consistent contractile responses, suggesting that voltage gated Ca2+ channels (VGCCs) are not activated in a basal situation in placental veins; (2) the increase of 5-HT contraction by Bay K 8644 may be produced by either the capability of this amine to depolarize the membrane of smooth muscle cells and subsequent facilitation of Ca2+ influx through VGCCs or direct activation by Bay K 8644 of receptor (5-HT) operated Ca2+ channels (ROCs), and (3) the increasing effect of Bay K 8644 appears to be due to a Ca2+ entry activation through VGCCs.
摘要
本研究的目的是分析在人胎盘静脉段中，钙离子通道激动剂Bay K 8644（0.1微摩尔）、钙离子通道拮抗剂硝苯地平（0.1微摩尔）和地尔硫䓬（1微摩尔）对血管收缩性和45钙离子摄取的影响。2. 钙离子通道激动剂Bay K 8644（0.1微摩尔）引起小幅度的浓度依赖性收缩，用7.5毫摩尔钾进行适度膜去极化可增强这种收缩。硝苯地平和地尔硫䓬可逆转这种增强作用。向先前用75毫摩尔钾去极化并暴露于无钙培养基的静脉段中添加钙离子会引起收缩反应，0.1微摩尔Bay K 8644可增强这种反应；这种增强被0.1微摩尔硝苯地平和1微摩尔地尔硫䓬阻断。3. 钾离子和5-羟色胺诱导浓度依赖性收缩反应，Bay K 8644（0.1微摩尔）可增强这种反应。0.1微摩尔硝苯地平和1微摩尔地尔硫䓬均抑制Bay K 8644的增强作用。Bay K 8644（30纳摩尔和0.1微摩尔）使45钙离子积累相对于基础值增加，钾离子（7.5、15和30毫摩尔）膜去极化可增强这种增加，而硝苯地平（0.1微摩尔）可抑制。钾离子（15和30毫摩尔，但不是7.5毫摩尔）和5-羟色胺（1微摩尔）诱导基础水平以上的45钙离子摄取，Bay K 8644（0.1微摩尔）可增强这种摄取。这种增加被硝苯地平（0.1微摩尔）拮抗。4. 这些数据表明：（1）Bay K 8644要产生一致的收缩反应需要用钾离子进行小幅度去极化, 这表明在胎盘静脉的基础状态下电压门控钙离子通道（VGCCs）未被激活；（2）Bay K 8644增强5-羟色胺收缩可能是由于这种胺使平滑肌细胞膜去极化并随后促进钙离子通过VGCCs内流的能力，或者是Bay K 8644直接激活受体（5-羟色胺）操纵的钙离子通道（ROCs），以及（3）Bay K 8644的增强作用似乎是由于通过VGCCs激活钙离子内流。
